Introduction to Nanoemulsions

Nanoemulsions are a variety of nanoparticle that can be used to disperse the oily cannabis extracts into water-based solutions. Solubilizing the oil in water, in and of itself, does not change the effect of the cannabis; It does, however, allow for a variety of products including cannabis beverages. Conceptually, the oil in the water is broken up into smaller and smaller sized droplets in order to become more and more dispersed in solution. In time, and without further mixing, the oil will separate out unless stabilized with surfactants. Surfactants effectively ‘protect’ the oil droplets and keep them separated from each other; preventing them from coming together to form larger particles and eventually a separate oil layer like in your Italian salad dressing. The challenge is to find a method and a surfactant that does not taste like soap!

The pharmacokinetic profile is how the molecule acts in the body. In the case of nanoemulsions, this is used to manipulate how much reaches your blood stream how quickly. With a traditional cannabis oil, absorption is highly variable and is affected by whether or not, and what types of food you have eaten and the extent to which the cannabinoids break down prior to being absorbed. Food will delay your stomach emptying the oil to where it will be absorbed, but fat in your meal will help the cannabis oil to be absorbed. This explains part of the reason that oral cannabis oil can be unpredictable!

Nanoemulsions are designed to survive the acids found in your stomach and to reliably reach the part of your gut where absorption occurs. Transmucosal absorption (absorption through the lining of the mouth) is present with some formulations of cannabinoids and may represent a future use of nanoemulsions. Nanoemulsions can also be used to improve the absorption of transdermal (through the skin) preparations. There is even research looking at using nanoemulsions for intravenous, nasal and pulmonary (lung) formulations.

Once the cannabis is in your body, it will be broken down by the same mechanisms as traditional oral cannabis oil, meaning you would not expect a significantly longer high from a nanoemulsion, other than if you get a higher dose into your system, it will naturally take longer for your body to clear it completely. Oral cannabis produces a longer “high” than inhaled cannabis due to the conversion of THC to 11-OH-THC by the liver’s CYP 450 enzyme system. 

Nanoemulsion droplets are formed most often by taking large oil drops in water and splitting them further and further down, in the presence of a surfactant, until they become 20 to 100 nm in size (a red blood cell is ~5,000 nm; a human hair is ~1,000,000 nm). There are a variety of methods to disrupt the droplets into smaller sizes, each with their own benefits and drawbacks. Conceptually, each approach requires a large amount of energy to be applied to the oil, water and surfactant system in order to break apart the particles to become nano-sized.

One such method, called sonication, uses high frequency sound waves to agitate the oil and disrupt it into smaller particles. This method is very scalable and is used extensively in industrial applications for nanoemulsion production. By varying the frequency and duration of the sonication, different sized particles can be achieved. Drawbacks include particle size variability, which difficult to control, and increases in temperature as a result of the process.

Another way to break up emulsion droplets into a nanoemulsion involves forcing the mixture through a reaction chamber at high pressure, which is essentially a narrowing space with a series of tight corners and narrow “Y” intersections. The collision of streams and the direction changes break up the particles into smaller sizes. This method is called high-pressure homogenization or microfluidization. It is scalable and tuneable by varying the pressure and the number of passes through the chamber to achieve different particle sizes. Heat is also created as a by-product and its effects need to be mitigated and accounted for when designing the nanoemulsion.

Continuing with high energy approaches, extrusion is a popular means to break particles into nano-sized droplets. In this instance, the large particles are forced through a membrane that has a specific pore size. As the mixture is pushed through the membrane, the emulsion drops are broken into pore-sized droplets. Size can be adjusted by varying the number of passes through the membrane and by changing the membrane. This method is somewhat scalable with process development but it has a reputation for creating particles that are not all equally sized (they have a large size distribution).

Other high energy methods include different mixing techniques using specifically designed high-shear blenders, or combinations of the aforementioned technologies.

In the above examples, the nanoemulsions are created by reducing the size of larger particles which is termed a top-down approach. By building the nanoparticles from the ground up (bottom-up method), there exists the possibility of using less energy, eliminating the effects of heat on the mixture, and enabling tighter control of the process for improved size tuning, size distribution and repeatability. Microfluidic mixing provides these benefits to nanoemulsion formulation. Within a micrometer channel that brings together two fluid paths, the excipients and payload of the nanoemulsion are brought together at specific flow rates. The minuscule mixing environment creates a condition where particles self-assemble due to the interaction of the hydrophilic (water ‘liking’) and lipophilic (oil ‘liking’) constituents of the formulation. Particles are spontaneously formed with no need to break them down further. Flow rates and mixing parameters enable very repeatable tuning of particle size, while size distribution is extremely narrow as compared to other methods. Microfluidic mixing does require more post-processing of the particles and scaling provides some challenges.

Nanoemulsion technology is the future of cannabis formulations. Using a variety of techniques, each with their own advantages, allows for the creation of products not seen on the market today. By creating specifically targeted pharmacokinetic profiles, the consumer receives a product with superior bioavailability and predictability. While the use of nanoemulsions with cannabis is relatively new, as research continues, it will quickly expand as customers and patients experience the benefits that this technology can offer.